Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical in vivo study.

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Synchrotron Analysis of Damaged Extraction Sockets Augmented Using a Synthetic Bone Block: A Pilot Study.

This study aimed to investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. Four participants were included, and socket augmentation was performed using SBB and a collagen membrane. Intraoral and CBCT scans were performed before extraction (baseline), immediately postoperative (IP), and at 6 months postoperative (6M). At 6M, a trephine biopsy sample was obtained during implant placement, and the sample was observed using synchrotron. Soft tissue profile changes were assessed using profilometric analysis of the intraoral scan data, while dimensional changes in hard tissue were evaluated based on CBCT measurements. Bone quality was analyzed using synchrotron imaging. There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11 ± 1.08 mm3, 0.02 ± 0.8 mm3, and -0.65 ± 0.82 mm3, respectively). Horizontal bone width was measured at 1-mm increments from the augmented bone crest to 5 mm apically and revealed only a slight reduction (< 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21 ± 0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage of new bone: 16.49% ± 4.91%). Socket augmentation using SBB appears to be a viable technique for regenerating damaged extraction sockets, with the augmented ridge dimensions maintained up to 6M. Further long-term randomized clinical trials are needed.

Risk of post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants: a cohort study using the common data model.

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Synchrotron Analysis of Damaged Extraction Sockets Augmented Using a Synthetic Bone Block: A Pilot Study.

AIM: To investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. MATERIALS AND METHODS: Four participants were included in whom socket augmentation was performed using SBB and a collagen membrane. Intraoral scan (IOS) was performed before extraction (baseline), immediately postoperative (IP), and at 6 months (6M). Cone-beam computed tomography (CBCT) was performed at IP and 6M. At 6M, a trephine biopsy was obtained during implant placement and the sample was observed using synchrotron. Profilometric change of soft tissue was measured from the IOS data, hard tissue dimensional change was measured from the CBCT data and the bone quality from synchrotron data. RESULTS: There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11±1.08 and 0.02±0.8, and -0.65±0.82 mm3). Horizontal bone width measured at 1 mm increments from the augmented bone crest to 5 mm apically revealed only slight reduction (less than 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21±0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage new bone = 16.49±4.91). CONCLUSIONS: Augmentation of the damaged extraction socket using SBB is a viable technique, in which the dimensions of the augmented ridge can be maintained up to 6M. Further long term randomized clinical trial is needed.

FasL is a catabolic factor in alveolar bone homeostasis.

AIM: Fas ligand (FasL) belongs to the tumour necrosis factor superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Faslgld mice has been reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown. MATERIALS AND METHODS: We performed a phenotypical analysis of mice carrying the homozygous Faslgld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, micro-computed tomography analysis revealed the distance between the cement enamel junction and the alveolar bone crest. Additional structural parameters, such as the bone volume fraction (BV/TV) and the periodontal ligament space volume, were measured. Histological analyses were performed to visualize the catabolic changes at the defect site. RESULTS: Healthy Faslgld mice were found to have more periodontal bone than their WT littermates. Faslgld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the inter-proximal bone in both strains. CONCLUSIONS: Our findings suggest that FasL is a catabolic factor in alveolar bone homeostasis but it does not affect the inflammatory osteolysis.

Does the fixture thread depth affect the accuracy of implant placement during fully guided immediate implant placement?: A human cadaver study.

BACKGROUND: The fixture thread depth reportedly influences the primary stability of dental implant, but its effect on the positional accuracy in immediate implant placement has not been reported previously. MATERIALS AND METHODS: Fifty-six single-rooted, anterior and premolar teeth were extracted from six human cadavers, followed by installing either regular-threaded implants (RT group, N = 30) or deep-threaded implants (DT group, N = 26) completely relying on the surgical guide. Optical impressions taken after osteotomy and fixture installation were superimposed with the preoperative virtual planning data to measure the vertical, angular, platform and apex deviations that occurred during osteotomy and installation. RESULTS: While the osteotomy deviations were similar between the two groups, the angular and apex deviation of the DT group (2.67 ± 2.56°; 1.04 ± 0.49 mm, respectively) were significantly larger than those of the RT group (1.61 ± 1.04°; 0.67 ± 0.41 mm, respectively) during installation (p < .05). When the installation deviations were analysed in the anterior and premolar areas separately, the angular, platform and apex deviations of the DT group (3.05 ± 3.26°; 0.75 ± 0.32 mm; 1.08 ± 0.56 mm, respectively) were significantly larger than those of the RT group (1.56 ± 0.73°, 0.59 ± 0.28 mm; 0.62 ± 0.38 mm, respectively) in the anterior site (p < .05), whereas there was no significant intergroup difference in the premolar site. CONCLUSION: In immediate-implant surgery, using an implant with a deeper thread might increase the deviations during installation, especially in the anterior area.

Platelet-rich fibrin combined with a particulate bone substitute versus guided bone regeneration in the damaged extraction socket: An in vivo study.

AIM: It has been proposed that platelet-rich fibrin (PRF) can be used to support bone regeneration during alveolar ridge augmentation. The aim of this study was to determine whether an approach utilizing PRF provides similar performance to the established guided bone regeneration (GBR) procedure. MATERIALS AND METHODS: Two-wall defects were surgically created in beagle dogs and treated in three experimental groups: (i) a sticky bone (SB) substitute prepared using liquid PRF and deproteinized porcine bone mineral (DPBM); (ii) SB covered with solid PRF compressed into a membrane; and (iii) GBR performed using DPBM covered by a collagen membrane. Quantitative reverse-transcription polymerase chain reaction was applied to the specimen after 1 week of healing, and microcomputed tomography (micro-CT) and histological outcomes were analysed after 8 weeks of healing. RESULTS: Compared with GBR, PRF resulted in a moderate increase in the expression levels of osteoblast and osteoclast markers, osteocalcin, and calcitonin receptor. Moreover, PRF modestly increased angiogenesis and the inflammation markers vascular endothelial growth factor (VEGF) and IL-6. Micro-CT and histological analyses confirmed the expected increased alveolar ridge area, with no significant differences between the three groups. Consistently, graft consolidation, as indicated by new bone formation at the defect site, did not differ significantly between groups. CONCLUSIONS: The present results demonstrate that PRF-based approaches perform comparably to the established GBR procedure in terms of the consolidation of DPBM in two-wall alveolar defects.

Vertical ridge augmentation feasibility using unfixed collagen membranes and particulate bone substitutes: A 1- to 7-year retrospective single-cohort observational study.

AIM: To determine whether vertical ridge augmentation (VRA) can be obtained through guided bone regeneration (GBR) using exclusively resorbable collagen membranes and particulate bone substitutes without additional stabilization. MATERIALS AND METHODS: This study retrospectively examined 22 participants who underwent VRA with staged or simultaneous implant placement. The vertical defects of all participants were filled with particulate bone substitutes and covered with resorbable collagen membranes. The augmented sites were stabilized with unfixed collagen membranes and the flap without any additional fixation. The augmented tissue height was assessed using cone-beam computed tomography at baseline, immediately after surgery, and at annual follow-ups. RESULTS: The vertical bone gain of the 22 augmented sites amounted to 6.48 ± 2.19 mm (mean ± SD) immediately after surgery and 5.78 ± 1.72 mm at 1- to 7-year follow-up. Of the 22 augmented sites, 18 exhibited changes of less than 1 mm, while the other 4 showed changes of greater than 1 mm. Histological observation of three representative cases revealed new bone apposition on the remaining material. CONCLUSION: The present findings indicate that GBR procedures using exclusively collagen membranes and particulate biomaterials without any additional fixation are feasible options for VRA.

Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ±â€¯15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ±â€¯33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.

Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population.

OBJECTIVE: This study aimed to determine the frequency of pathogenic NOTCH3 variants among Koreans. METHODS: In this cross-sectional study, we queried for pathogenic NOTCH3 variants in 2 Korean public genome databases: the Korean Reference Genome Database (KRGDB) and the Korean Genome Project (Korea1K). In addition, we screened the 3 most common pathogenic NOTCH3 variants (p.Arg75Pro, p.Arg544Cys, and p.Arg578Cys) for 1,000 individuals on Jeju Island, where the largest number of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported in Korea. RESULTS: The pathogenic NOTCH3 variant (p.Arg544Cys) was found in 0.12% of sequences in the KRGDB, and 3 pathogenic variants (p.Arg75Pro, p.Arg182Cys, and p.Arg544Cys) were present in 0.44% of the Korea1K database. Of the 1,000 individuals on Jeju Island, we found 2 cysteine-altering NOTCH3 variants (p.Arg544Cys variant in 9 and p.Arg578Cys in 1 individual) in 1.00% of the participants (95% confidence interval: 0.48%-1.83%). The presence of cysteine-altering NOTCH3 variants was significantly associated with a history of stroke (p < 0.001). DISCUSSION: Pathogenic NOTCH3 variants are frequently found in the general Korean population. Such a high prevalence of pathogenic variants could threaten the brain health of tens of thousands to hundreds of thousands of older adults in Korea.

Immediate loading protocols increase the risk of failure of implants placed by fully guided surgery in partially edentulous jaws: A randomized clinical trial.

AIM: To compare the 1-year outcomes of immediate loading (IL) and delayed loading (DL) protocols for implants placed by fully guided surgery in partially edentulous jaws. MATERIALS AND METHODS: This study included 72 patients who received implant surgery with either IL (93 implants, 36 patients) or DL (94 implants, 26 patients). A prefabricated provisional prosthesis was delivered immediately for the IL group (86 implants, 32 patients) with the exception of 4 subjects in whom an initial torque of >20 Ncm and an implant stability quotient of >65 were not achieved, while all DL-group implants were loaded after 3 months. The 1-year implant survival rate estimated by intention-to-treat (ITT) and per-protocol (PP) analyses, and the marginal bone loss (MBL) estimated by cone-beam computed tomography were statistically evaluated (p < 0.05). RESULTS: The survival rate in the DL group was 100% at both patient and implant levels. With only 26 subjects with 78 implants surviving in the IL group, the survival rates were 69.4% and 83.4% at the patient and implant levels, respectively, in the ITT analysis, and 78.1% and 90.2% in the PP analysis. All intergroup differences in survival rates were statistically significant (p < 0.01). MBL was less than 0.1 mm in both groups (p > 0.05). CONCLUSIONS: IL for implants placed by fully guided surgery in the partially edentulous jaws increased the probability of failure compared to 3-month DL. Regardless of when loading occurred, marginal bone levels remained stable.

Addition of autogenous bone chips to deproteinized bovine bone mineral does not have additional benefit in lateral ridge augmentation-A preclinical in vivo experimental study.

OBJECTIVE: To compare the outcome after extensive lateral guided bone regeneration using deproteinized bovine bone mineral (DBBM) with or without autogenous bone chips in a canine model of chronic horizontal alveolar ridge defect. MATERIALS AND METHODS: The second, third and fourth lower premolars of both sides were extracted, and the buccal bone walls were completely removed in five beagle dogs. After 4 weeks, DBBM particles mixed with autogenous bone chips at a ratio of 1:1 were grafted at one side (DBBM/Auto group), while DBBM particles alone were grafted at the contralateral side (DBBM group). The graft materials on both sides were covered by a resorbable collagen membrane and fixation pins. Microcomputed tomographic volume and histomorphometric analyses were performed at 16 weeks post-surgery. RESULTS: The ridges of both groups were recovered horizontally, but new bone formation beyond the original ridge contour at the defect site was not found. The DBBM group exhibited a larger total radiographic augmented volume and new bone volume compared with the DBBM/Auto group, but the differences were minimal (p > .05). Histologically, the regenerated area and new bone area were also slightly larger without any statistical significance in the DBBM group than in the DBBM/Auto group (p > .05). CONCLUSION: The addition of autogenous bone chips to DBBM for lateral ridge augmentation may confer no advantage over grafting DBBM alone with respect to both space maintenance and de novo bone formation in dogs.

FasL Is Required for Osseous Healing in Extraction Sockets in Mice.

Fas ligand (FasL) is a member of the tumor necrosis factor (TNF) superfamily involved in the activation of apoptosis. Assuming that apoptosis is initiated after tooth extraction it is reasonable to suggest that FasL may play a pivotal role in the healing of extraction sockets. Herein, we tested the hypothesis of whether the lack of FasL impairs the healing of extraction sockets. To this end, we extracted upper right incisors of FasL knockout (KO) mice and their wildtype (WT) littermates. After a healing period of two weeks, bone volume over total volume (BV/TV) via µCT and descriptive histological analyses were performed. µCT revealed that BV/TV in the coronal region of the socket amounted to 39.4% in WT and 21.8% in KO, with a significant difference between the groups (p=0.002). Likewise, in the middle region of the socket, BV/TV amounted to 50.3% in WT and 40.8% in KO (p<0.001). In the apical part, however, no difference was noticed. Consistently, WT mice displayed a significantly higher median trabecular thickness and a lower trabecular separation when compared to the KO group at the coronal and central region of the socket. There was the overall tendency that in both, female and male mice, FasL affects bone regeneration. Taken together, these findings suggest that FasL deficiency may reduce bone regeneration during the healing process of extraction sockets.

Invasive dental procedures as risk factors for postoperative spinal infection and the effect of antibiotic prophylaxis.

AIM: To identify invasive dental procedures as a risk factor for postoperative spinal infection (PSI) and evaluate the effectiveness of antibiotic prophylaxis. MATERIALS AND METHODS: We analysed 229,335 patients who underwent spinal surgery with instrumentation from 2010 to 2017, using the nationwide database. The incidence of spinal infection 2 years after surgery was determined. Invasive dental procedures as a risk factor for PSI and the effects of antibiotic prophylaxis during this period were also analysed. RESULTS: A total of 15,346 patients (6.69%) were diagnosed with PSI. It was found that advanced age, male sex, and a high Charlson Comorbidity Index were risk factors for PSI. The risk of PSI did not increase following dental procedures (adjusted hazard ratio [HR] 0.850; 95% confidence interval [CI], 0.793-0.912) and was not affected by antibiotics (adjusted HR 1.097; 95% CI, 0.987-1.218). Patients who received dental treatment as early as 3 months after spinal surgery had the lowest risk of postoperative infection (adjusted HR 0.869; 95% CI, 0.795-0.950). CONCLUSIONS: Invasive dental procedure does not increase the risk of PSI, and antibiotic prophylaxis before dental procedure was not effective in preventing spinal infection.

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines.

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

Diverse patterns of bone regeneration in rabbit calvarial defects depending on the type of collagen membrane.

PURPOSE: Various crosslinking methods have been introduced to increase the longevity of collagen membranes. The aim of this study was to compare and evaluate the degradation and bone regeneration patterns of 3 collagen membranes. METHODS: Four 8-mm-diameter circular bone defects were created in the calvaria of 10 rabbits. In each rabbit, each defect was randomly allocated to 1) the sham control group, 2) the non-crosslinked collagen sponge (NS) group, 3) the chemically crosslinked collagen membrane (CCM) group, or 4) the biphasic calcium phosphate (BCP)-supplemented ultraviolet (UV)-crosslinked collagen membrane (UVM) group. Each defect was covered with the allocated membrane without any graft material. Rabbits were sacrificed at either 2 or 8 weeks post-surgery, and radiographic and histologic analyses were done. RESULTS: New bone formed underneath the membrane in defects in the CCM and UVM groups, with a distinctive new bone formation pattern, while new bone formed from the base of the defect in the NS and control groups. The CCM maintained its shape until 8 weeks, while the UVM and NS were fully degraded at 8 weeks; simultaneously, sustained inflammatory infiltration was found in the margin of the CCM, while it was absent in the UVM. In conclusion, the CCM showed longer longevity than the UVM, but was accompanied by higher levels of inflammation. CONCLUSIONS: Both the CCM and UVM showed distinctive patterns of enhancement in new bone formation in the early phase. UV crosslinking can be a biocompatible alternative to chemical crosslinking.

Transcriptomic profiles and their correlations in saliva and gingival tissue biopsy samples from periodontitis and healthy patients.

PURPOSE: This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool. METHODS: Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels. RESULTS: There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types. CONCLUSIONS: The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.

Clinical factors influencing implant positioning by guided surgery using a nonmetal sleeve template in the partially edentulous ridge: Multiple regression analysis of a prospective cohort.

OBJECTIVE: To determine the positional accuracy of implants placed with a three-dimensionally printed template having nonmetal sleeves and to determine the contributing factors to observed deviations. MATERIALS AND METHODS: One hundred and eighty-seven implants placed in 72 patients were analyzed. Presurgical intraoral scans and cone-beam computed tomography images obtained before and after surgery were superimposed, and vertical, angular, platform, and apex deviations were measured between the virtually planned and actually placed positions. A multiple linear regression model was designed for identifying the contributing factors. Statistical significance was set at p < .05, with Bonferroni correction if necessary (p < .0167). RESULTS: A total of 187 implants demonstrated deviations of 0.65 [0.56, 0.75] mm (mean [95% confidence interval]) vertically, 3.59° [3.30°, 3.89°] angularly, 1.16 [1.04, 1.28] mm at platform, and 1.50 [1.36, 1.65] mm at apex. Implants placed in the mandible showed larger angular, platform, and apex deviations compared with those in the maxilla (p = .049, p = .014 and p = .003, respectively). Implants placed at the third or fourth nearest sites from the most-distal tooth had larger deviations than those placed at the first or second nearest sites, in vertical, platform, and apical aspects (p = .015, p = .011 andp = .018, respectively). This was only applicable to free-ending-supported templates (p < .0167), and anchor pin-supported free-ending templates (p < .0167). CONCLUSION: Using a three-dimensionally printed surgical template with a nonmetal sleeve in the partial edentulous ridge resulted in larger deviations in implants placed in the mandible or distal free-end third or fourth nearest site.

Oral Fluid Biomarkers for Diagnosing Gingivitis in Human: A Cross-Sectional Study.

Diagnoses based on oral fluid biomarkers have been introduced to overcome limitations of periodontal probe-based diagnoses. Diagnostic ability of certain biomarkers for periodontitis have been identified and widely studied, however, such studies targeting gingivitis is scarce. The aims of this study were to determine and compare the efficacies and accuracies of eight biomarkers in diagnosing gingivitis with the aid of receiver operating characteristic (ROC) curves. The probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were examined in 100 participants. Gingival crevicular fluid was collected using paper points, and whole-saliva samples were collected using cotton roll. Samples were analyzed using enzyme-linked immunosorbent assay kits for the different biomarkers. The levels of matrix metalloproteinase (MMP)-8, MMP-9, lactoferrin, cystatin C, myeloperoxidase (MPO), platelet-activating factor, cathepsin B, and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen were analyzed. MPO and MMP-8 levels in saliva were strongly correlated with gingivitis, with Pearson's correlation coefficients of 0.399 and 0.217, respectively. The area under the curve (AUC) was largest for MMP-8, at 0.814, followed by values of 0.793 and 0.777 for MPO and MMP-9, respectively. The clinical parameters of GI and PI showed strong correlations and large AUC values, whereas PD and CAL did not. MMP-8 and MPO were found to be effective for diagnosing gingivitis. Further investigations based on the results of this study may identify clinically useful biomarkers for the accurate and early detection of gingivitis.

Continuous Label-Free Electronic Discrimination of T Cells by Activation State.

The sensitivity and speed with which the immune system reacts to host disruption is unrivaled by any detection method for pathogenic biomarkers or infectious signatures. Engagement of cellular immunity in response to infections or cancer is contingent upon activation and subsequent cytotoxic activity by T cells. Thus, monitoring T cell activation can reliably serve as a metric for disease diagnosis as well as therapeutic prognosis. Rapid and direct quantification of T cell activation states, however, has been hindered by challenges associated with antigen target identification, labeling requirements, and assay duration. Here we present an electronic, label-free method for simultaneous separation and evaluation of T cell activation states. Our device utilizes a microfluidic design integrated with nanolayered electrode structures for dielectrophoresis (DEP)-driven discrimination of activated vs naïve T cells at single-cell resolution and demonstrates rapid (<2 min) separation of T cells at high single-pass efficiency as quantified by an on-chip Coulter counter module. Our device represents a microfluidic tool for electronic assessment of immune activation states and, hence, a portable diagnostic for quantitative evaluation of immunity and disease state. Further, its ability to achieve label-free enrichment of activated immune cells promises clinical utility in cell-based immunotherapies.